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"In both cases, the compositions, methods and uses inhibit one or more steps or stages necessary for a productive or ongoing viral infection, including inhibiting viral entry. Preferably, the compositions, methods and uses inhibit viral replication and/or spread, such as inhibiting one or more steps of viral transcription, translation, assembly, packaging and/or egress within or from an infected host cell, such as a mammalian or human cell. The invention therefore preferably limits or substantially confines viral infections to initially infected cells and cell populations, thus substantially inhibiting or preventing the subsequent or ongoing infection of additional host cells or tissues."

"As the invention inhibits one or more steps or stages necessary for productive or ongoing infection common to all viruses, the anti-viral methods and uses of the invention are suitable for treating all viruses, both enveloped and non-enveloped viruses, including those that infect plants, animals, vertebrates, mammals and human patients. The invention is suitable for treating all viruses that infect vertebrates, as listed herein in Table H, particularly humans, and particularly viruses that are pathogenic in animals and humans. The viral infections and associated and resultant diseases that can be treated by the invention include those viruses and diseases set forth in Table J, as exemplified by treating CMV, RSV, arenavirus and HIV infections, and the diseases hepatitis, influenza, pneumonia, Lassa fever and AIDS. "

If you read this patent (it's long), remember 3g4 is in clinical trials for combo hepc/hiv.

The patent focuses on two antibodies (3g4 and 9d2) both are anti-ps antibodies with the 3g4 antibody seemingly the preferred. Remember that these antibodies are the "guidance system that directs the payload". Both of these antibodies can be armed with almost any nrti, nnrti and pi to do the job. The fact that the payload is target- directed, substantially, lowers the risk of AEs.

Of course these antibodies can be directed to cancers also (ie: KS, lung etc) with a different payload. Currently in phase 2 clinical trials for cancer with the 3g4 antibody.

Steve King, CEO of Peregrine Pharm., answers a question concerning Bavi and hiv therapeutic, hinting at the data they are seeing in the hep/c/ Hiv trial:

"Any thought on possibly moving forward with a drug cocktail in HIV as well? Obviously what the data shows but –

Steve King

Yeah, I think we'll let the data drive that discussion. But I think absolutely. Again Bavi is really designed if you will for combination therapy with direct antivirals in the infectious disease area."

Steve King, CEO of Peregrine Pharm., answers a question concerning Bavi and hiv therapeutic, hinting at the data they are seeing in the hep/c/ Hiv trial:

"Any thought on possibly moving forward with a drug cocktail in HIV as well? Obviously what the data shows but –

Steve King

Yeah, I think we'll let the data drive that discussion. But I think absolutely. Again Bavi is really designed if you will for combination therapy with direct antivirals in the infectious disease area."

Bavi is the guided missle, ARVs are the payload (perhaps antibodies also, as being studied by CHAVI). The ARVs can be attached to bavi (see posts above) to enhance the effectiveness of the therapy and diminish AEs. I know the patent is a long read, but there is a lot of neat information contained within the patent that explains the MOA.

This power point presentation was showcased at the International AIDS vaccine conference in Atlanta during sept. Dr. Gary Nabel of CHAVI was the presenter. The same antibodies used for a preventative vaccine can also be used as a therapeutic. The pathway is becoming focused. Is there light at the end of the tunnel? It seems so.

The following video was suggested to me by YouTube--obviously because I've watched other HIV videos there. I know, of course, this has all been discussed here--A3G and Vif. Has this video been shown? Very interesting. Sometimes it is easier for me to understand things when produced on video than reading research papers.

Consortium Assembled to Design Human Trials of Mosaic HIV VaccineMichelle GailiunDuke University Medical Center michelle.gailiun@duke.eduOctober 18, 2010An international team of scientists will design and implement the first human trial of a mosaic HIV vaccine candidate, a novel strategy that attempts to counter one of the most daunting challenges in HIV vaccine design: the virus's extensive genetic diversity.Traditional HIV vaccines are designed to stimulate the body's immune system to recognize naturally occurring stretches of specific amino acids in the virus's proteins. In contrast, mosaic vaccines are composed of many sets of synthetic, computer-generated sequences of proteins that can prompt the immune system to respond to a wide variety of circulating HIV strains.Such vaccines have already been studied in animals and have shown some success in enhancing the breadth of immune responses. Now, Barton Haynes, MD, director of the Duke Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology (CHAVI), says a newly formed research coalition has begun designing an early phase safety trial to assess mosaic vaccines in humans. The trial will test the mosaic concept and could possibly lead to the next generation of HIV vaccine candidates.Haynes, who will lead the consortium, says the group will use the NYVAC vaccinia vector (derived from the vaccine to protect against smallpox) and DNA that contain a new set of artificial computer-designed HIV genes in a phase I clinical trial that will be supported by the Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.Haynes says the consortium hopes to launch human trials by late 2012.The consortium includes many of the world's leading researchers and organizations committed to finding an effective vaccine to protect against HIV infection, including the Foundation for the National Institutes of Health, the Fred Hutchinson Cancer Research Center and its NIH-funded HIV Vaccine Trials Network, the IPPOX Foundation in Switzerland, Beth Israel Deaconess Medical Center, Los Alamos National Laboratory, the NIH/NIAID Vaccine Research Center, Duke University and its Center of HIV/AIDS Vaccine Immunology, the Bill & Melinda Gates Foundation and the Division of AIDS of the National Institute of Allergy and Infectious Diseases.Bette Korber, a senior scientist at Los Alamos National Laboratory and leader of the team that developed the mosaic genes, noted "HIV's diversity is vast, and the mosaic gene design represents a novel vaccine design to directly tackle HIV diversity in human clinical trials. Based on computational models, mosaic vaccines were predicted to perform better than natural HIV genes; experimental studies in animals that directly compared mosaic to natural vaccines supported that prediction. We are excited to test this concept in humans.""Each member of this consortium is also a member of the Global HIV Vaccine Enterprise, and this collaboration is truly a global effort to make progress on HIV vaccine development," said Haynes.The NYVAC vaccine is being provided by Sanofi-Pasteur, which is a collaborator in the study. The clinical development of NYVAC HIV vaccines has to date been conducted in Europe primarily through the EuroVacc Program.

I don't think the final protocols for the trial have been developed yet. The good news is that the vaccine is a mosaic candidate that will attempt to attack the virus's extensive genetic diversity and hopefully respond to a wide variety of the (circulating ) viral strains. This approach has never been tried before. We'll have to see what develops.

Results, hopefully, will be published in June. Could Hepc have a kinder and gentler therapy in the making?What about other retro-viruses?

"Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases."

In prior HCV clinical trials, bavituximab administered as monotherapy also showed promising on therapy antiviral activity of up to 1.5 log viral load reduction. With limited resources Peregrine must really feel Bavi has a good shot at besting interferon's role in HCV treatment.Fantastic.

"Bavituximab is being developed by Peregrine Pharmaceuticals for use in both infectious diseases and oncology. This is an anti-phosphatidylserine-targeted monoclonal antibody. As Steven King, CEO, explained, “Phosphatidylserine is tightly bound to dead and dying cells and is one of the best tumor markers we’ve found.” The immune system down-regulates in its presence, effectively allowing cancer and infectious diseases to slip past the immune system undetected. By targeting phosphatidylserine, “Bavituximab has the potential to be a broad spectrum agent against every virus we’ve looked at,” he concluded"

Could this be why the US govt is looking so closely at Bavi? What is CHAVI doing with anti-ps and why did they make Dr. Thorpe's lab part of their group? I wonder how bavi faired in the hepc/hiv trial?

"Completion of enrollment in our third Phase I HCV trial is an important milestone for our bavituximab antiviral program, and sets the stage for reporting clinical data at a medical conference in the second quarter of this year while we begin to evaluate combination treatment with the antiviral agent ribavirin in a recently initiated study," said Steven W. King, president and chief executive officer of Peregrine. "Though standard treatment for chronic HCV may soon evolve with the introduction of new targeted antiviral drug candidates, immune stimulation with interferon remains a critical component of therapy. Preclinical data support the potential combination of bavituximab and ribavirin and we look forward to seeing how this combination initially compares to standard interferon and ribavirin treatment for 12 weeks in our Phase II study for patients infected with HCV."

In prior HCV clinical trials, bavituximab administered as monotherapy in single and multiple doses demonstrated a positive safety profile with no dose-limiting toxicities or serious adverse events. Bavituximab as a monotherapy also showed promising on therapy antiviral activity of up to 1.5 log viral load reduction.

Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen.

About the Phase Ib HCV TrialPeregrine's open-label, dose escalation safety study is designed to assess the safety and of bavituximab in up to 24 patients chronically infected with HCV and HIV. Patient cohorts received ascending dose levels of bavituximab weekly for up to 8 weeks. Primary endpoints include safety and pharmacokinetics, and secondary endpoints will measure HCV and HIV RNA by PCR. For further information about Peregrine's HCV trials, please visit www.peregrinetrials.com or http://www.clinicaltrials.gov/ct2/results?term=bavituximab.

About HCVAccording to the U.S. Centers for Disease Control and Prevention, an estimated 3.2 million individuals in the United States have chronic hepatitis C virus (HCV) infection. Chronic HCV infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or death. It is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplant in the United States. Approximately 8,000 to 10,000 people die every year from HCV-related liver disease.

About Bavituximab's Antiviral ApproachBavituximab is the first in a new class of patented antibody therapeutics that target and bind to phosphatidylserine (PS), a specific phospholipid component of cell membranes. Bavituximab helps reactivate and direct the body's immune system to destroy infected cells and virus particles that exhibit this specific phospholipid on their surface. Since their target is host-derived rather than pathogen-derived, PS-targeting antibodies have the potential for broad-spectrum antiviral activity and are also expected to be much less susceptible to the viral mutations that often lead to drug resistance.

Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases.